The use of Hevea brasiliensis natural rubber latex (NRL) as a protective material has a long history of usage dating back to the 1800s. The widespread use of barrier NRL articles like gloves and condoms increased tremendously in the 1980s primarily due to the “universal precautions” policy outlined by the Centers for Disease Control. NRL's popularity and longevity can be attributed to several factors. The physical properties of NRL are superior to non-latex synthetic products. Field latex, the feedstock material for NRL that continues to be readily available in Malaysia and Thailand, is now available in several new regions around the world including India, Vietnam, Indonesia, Liberia, Guatemala, and China. NRL is significantly less expensive than most petroleum-based synthetic materials whose cost continues to fluctuate with the cost of crude oil. Additionally, the reduced environmental impact of natural rubber latex compared to petroleum-based synthetic materials continues to be the preferred material of choice in an environmentally conscious society. The availability, ease of production and the performance of NRL products continue to make NRL the chosen material by manufacturers and users among industry and medical professionals. Today, there are over 40,000 commercially available products made from NRL. A concern with NRL continues to be its potential involvement with adverse health effects due to the antigenicity of NRL products. An intuitive means of controlling this parameter in the NRL source material is by de-proteination/protein modification. Validation of this process can be achieved by specific methods of protein quantification.
Although the first description of an allergic reaction to latex gloves appeared in the American Literature in 1933 when usage was slight, the majority of latex allergic reactions were documented in the late 80s and throughout the 90s and 2000s. Published data indicate 17% of American healthcare workers and up to 73% or more of frequently exposed patients, such as those with spina bifida, were sensitized to latex proteins.
Several attempts, including new source crops, synthetic lattices and various treatment methods, have been made to eliminate these problem proteins from Hevea NRL by biological, physical and/or chemical methods that affect the complex acid-base behavior of proteins. One approach has been to introduce the latex articles to multiple leaching steps and chlorination. This approach does reduce the protein levels in the finished product; however it weakens the latex film thus compromising the physical properties of the product. Another attempt to reduce proteins in NRL is the use of proteolytic enzymes to degrade the proteins in the latex solution. The issue with this approach is the introduction of another protein (the enzyme) to the latex, which may itself be allergenic. The most logical solution is the use of low-protein latex, such as the treated NRL of the present invention as this approach will more than likely reduce the possibility for an allergic response in the end user of the finished product. If high levels of protein are not present in the raw material they cannot appear in the manufactured product.
Two other non-Hevea NRL materials have been attempted to be commercialized in the US; guayule rubber latex and Taraxacum kok-saghyz, also known as the Russian dandelion. These materials are reported to be higher in cost compared to natural rubber and presently are available only in limited quantities. Hevea NRL has been around for more than a century and its antigenic proteins have been thoroughly researched. The allergenic properties and economic viability of latex from the guayule & Taraxacum kok-saghyz have yet to be scrutinized in the way that Hevea has been. Being natural products, both of these materials have their own unique set of proteins with potential allergenic behavior not yet understood.
Recently, it has been shown that allergens are distributed into few protein families and possess a restricted number of biochemical functions. The allergen functions found most frequently were limited to hydrolysis of proteins, polysaccharides, and lipids; binding of metal ions and lipids; storage; and cytoskeleton association. The limited number of protein families that are allergenic and the narrow functional distribution of most allergens support the existence of yet unknown factors that render proteins allergenic. Many of these specific protein functions play into the chemistry used to manipulate them yielding a modified NRL source material.
The last decade and a half has seen a great change in latex use as a result of publicity concerning these allergies. Today in the U.S. there is almost universal awareness of the risks associated with repeated latex exposure, particularly in the healthcare fields where exposure is more profound. Awareness of the risks, however, extends into the industrial glove market, and even to the general public, who have received risk warnings from various government and health-watch groups. As a result there exists much interest in the market, fueling a strong trend to reduce exposure to latex-associated allergens.
Manufacturers have responded in several ways: I) reduction or elimination of donning powder, 2) utilization of chlorinated glove washing and additional processing steps to reduce antigenic protein load, 3) use of coatings to reduce actual contact with latex, and 4) introduction of alternative materials that mimic, natural latex performance characteristics. Each of these industry reactions represents compromises either from ease of use, performance, or cost standpoint. In short, nothing beats the tactile, comfort, and barrier protection that is provided by natural latex products.
In the last ten years there has been an increasing awareness of the possible immunologic and other reaction risks associated with the use of latex gloves. This awareness is the result of the proliferation in glove usage among healthcare workers in order to avoid potential exposure to HIV/AIDS transmission sources.
An increase in the reported incidence of latex allergic sensitivity and other skin reactions has been concomitant with increased glove usage. This has spurred an effort by industry leaders and manufacturers to reduce exposure to latex. Glove makers have initiated latex substitution in the manufacture of gloves, limited use of donning powder so as to prevent antigenic proteins leached into the cornstarch powder from becoming airborne (a source of respiratory exposure and subsequent sensitization), and the introduction of low protein methods for latexes to reduce the overall protein content of gloves.
Latex rubber in its natural form consists of polymeric, long chain molecules consisting of repeating units of isoprene:
When it is harvested from the rubber tree, Hevea brasiliensis, the liquid, sticky substance also contains proteins like heavamine, hevein, and rubber elongation factor. Although the basic isoprene polymer is non-antigenic, the associated proteins are highly antigenic. It is important to note this difference in order to minimize the antigenic impact of natural latex without destroying its underlying structure.
In its natural state, natural latex does not possess characteristics that are commercially useful. In order to achieve utilitarian value, including strength, elasticity, and memory, the chains of isoprene must be cross-linked to one another. Depending on the type of rubber end product desired, this is achieved with either application of heat and sulfur, or in the case of latex rubber used in the manufacture of gloves, various chemical accelerators that donate or bind sulfur, thus speeding the cross-linking process. The major accelerators are thiurams, mercaptobenzothiazoles (MBTs) and carbamates.
In addition to accelerators, latex glove manufacturers utilize another class of additives, called sensitizers, which most frequently consist of substituted phenols. These substances are used to impede oxidation, and resultant degradation, of natural latex.
Foreign materials, natural latex proteins, accelerators, and sensitizers can all provoke human reactions, but the allergenic reactions due to the proteins are considered to be the most problematic in the healthcare field. The following briefly describes three major types of foreign material reactions most commonly associated with latex use:
Irritant dermatitis is skin irritation that does not involve the body's immune response, that is, it is not an allergic response. Frequent hand washing and inadequate drying, aggressive scrubbing technique or detergents, mechanical abrasive effect of powder, climatic irritation, and emotional stress can all cause this condition. Even though this is not an allergic reaction, irritant hand dermatitis can cause breaks in the skin which can facilitate entry of the sensitizing latex protein or chemicals found in the commercial product, and in turn lead to latex allergy.
Delayed cutaneous hypersensitivity (type PV allergy) is contact (hand) dermatitis generally due to the chemicals used in latex production. It is mediated via T-cells causing a skin reaction that is typically seen 6-48 hours after contact. The reaction is local and limited to the skin that has contact with the glove. While not life threatening, those with type IV allergy are at increased risk to develop type I allergy. As in irritant dermatitis, the broken skin barrier can provide an entry site into the body for foreign materials. This can produce sensitization to latex proteins leading to a more serious type of reaction.
The third and potentially most serious type of reaction associated with latex use is a true IgE/histamine-mediated allergy to protein (also called immediate, or type I hypersensitivity). This type of reaction can involve local or systemic symptoms. Local symptoms include contact urticaria (hives), which appear in the area where contact occurred, i.e., the hands, but can spread beyond that area and become generalized. More generalized reactions include allergic rhinoconjunctivitis and asthma. The presence of allergic manifestations to natural latex indicates an increased risk for anaphylaxis, a rare but serious reaction experienced by some individuals who have developed an allergy to certain proteins (e.g., insect stings, natural rubber, penicillin). This type I reaction can occur within seconds to minutes of exposure to the allergen. When such a reaction occurs, it can progress rapidly from swelling of the lips and airways, to shortness of breath, and may progress to shock and death, sometimes within minutes. While any of these signs and symptoms may be the first indication of allergy, in many workers with continued exposure to the allergen, there is progression from skin to respiratory symptoms over a period of months to years. Some studies indicate that individuals with latex allergy are more likely than latex non-allergic persons to be atopic (have an increased immune response to some common allergens, with symptoms such as asthma or eczema). Once natural latex allergy occurs, allergic individuals continue to experience symptoms, which have included life-threatening reactions.
There are several classes of people known to be at increased risk for latex allergy. Medical patients who have had multiple hospitalizations and have been exposed numerous times to latex medical products, healthcare workers, and atopic individuals comprise this high-risk group. Current estimates are that 8-17% of healthcare workers become sensitized. Despite the recent emphasis on universal precautions, the marked increase in glove usage due to commutable disease prevention is largely blamed for the increase in latex allergies among these groups. Atopic individuals (those with other allergies or asthma) are at significantly greater risk to develop latex allergy than the general population. It is estimated that as many as 25-30% of atopic healthcare workers may become sensitized.
The problems presented by allergic reactions to latex are exacerbated by the proliferation and widespread use of latex-based products. Latex presents great risk to persons in the health care industry where latex products are used extensively in the form of gloves, casts, dressings, tapes, catheters, tubes, drains, airway management devices, med delivery, tourniquets, monitoring devices, and others. One persistent threat lies in the cornstarch powder used to lubricate and ease donning of rubber gloves. The proteins absorb onto the powder and become aerosolized during use and when the gloves are donned and removed.
Products containing latex are also found throughout the home in the form of balloons, art supplies, toys, swimming equipment, contraceptive devices, cosmetics, bottle nipples, pacifiers, clothing, chewing gum, rubber bands, and others. Groups at risk include particularly children with spina bifida, those who have been shown to have a very high risk of latex sensitivity, patients with congenital urologic abnormalities, healthcare providers and rubber industry workers.
Since the severe allergic reactions to latex are due to their naturally occurring proteins, the prior art offers little in the way of solutions. For example, ammonia treatment of the NRL proteins can cause breakdown and precipitation of some latex proteins, but the allergenicity appears to be preserved and other antigenic latex proteins are unextractable. In short, the literature recommends that the only treatment available for latex allergy is avoidance.
The Food and Drug Administration (FDA), as well as other state and federal agencies, has received requests to ban the use of glove powder. It has been suggested that experimental and clinical studies demonstrate that glove powder on medical gloves can enhance foreign body reactions, increase infections and act as a carrier of natural latex allergens. The National Institute of Occupational Safety and Health (NIOSH) recently issued a safety alert recommending the use of powder-free, reduced protein content latex gloves to reduce exposure to natural latex proteins (allergens).
Experimental and clinical data demonstrate that some NRL proteins are allergenic. Further, natural latex proteins bind to cornstarch while aerosolized powder on NRL gloves is allergenic and can cause respiratory allergic reactions. Published studies support the conclusion that airborne glove powder represents a threat to individuals allergic to NRL and may represent an important agent for sensitizing non-allergic individuals. There are also published data (although limited) and clinical experience that cornstarch powder on NRL gloves may also be a contributing factor in the development of irritation and type IV allergy.
In addition to dusting powder, other lubricants may also be used in the manufacturing process. Latex and some polymers are tacky and dipped products such as condoms and gloves made of these materials stick to the mold or former. A mold-release lubricant such as calcium carbonate or a mixture of calcium carbonate and cornstarch is used to enable the removal of these dipped products like condoms and gloves from molds. The other side of the dipped product may be coated with a donning lubricant, such as cornstarch or silicone oils, to make donning easier and to prevent dipped products from sticking during the manufacturing process.
Over the past three years, the FDA has received requests to ban the use of all glove powders. These requests have been based on repeated clinical and experimental studies reporting that cornstarch on surgical gloves can damage tissue's resistance to infection, enhance the development of infection, serve as a potential source of occupational asthma, and provide a source of natural latex protein exposure to natural latex allergic individuals. The issues regarding the use of glove powder, except for the transport of natural latex protein allergens, apply to the use of glove powder on both NRL and synthetic gloves. Several states, acting on their own initiative have banned the sale and use of glove powders.
Thus, there is a need to develop a NRL composition and method of making the same that can provide reduced allergenicity. It is an object of the present invention is to teach a method of reducing the allergenicity of NRL prior to vulcanization to enable the creation of a commercial product relatively free of allergenicity with no apparent loss of physical properties.